One of the greatest problems in the treatment of cancerous tumors is metastasis, i.e., the transmission of cells of the primary tumor to other locations in the patient and the establishment of new tumors at such locations. Metastasis is difficult to control because it often occurs before the primary tumor is diagnosed and treated. Also, the metastatic lesions may be locations which limit the effective dosages of the treatments, e.g., radiation, due to the sensitivity of the surrounding tissue to such treatments. Further, metastatic cells are heterogeneous and cells which are resistant to conventional therapy tend to emerge.
Conventional methods for treating metastasis include surgery, radiotherapy and/or chemotherapy. Other approaches which have been proposed include the use of monoclonal antibodies, hyperthermia, radiation sensitizing and protective drugs, and stimulated macrophages.
It has been reported that Fidler et al in "Macrophages and Cancer Metastasis" that macrophages can be stimulated to become tumoricidal. Tumoricidal macrophages have the ability to discriminate between metastatic or tumorigenic and normal cells. Thus, although tumor cells are heterogeneous, they are all susceptible to lysis by the activated macrophages.
Two pathways to achieve macrophage activation in vivo are disclosed. One pathway involves macrophage interaction with microorganisms or their products such as endotovins, the bacteria wall skeleton and small components of the bacteria cell wall, e.g., muramyl dipeptide. Another pathway for activating macrophages involves the interaction of macrophages with soluble mediators released by sensitized lymphocytes, e.g., soluble lymphokine.
Each of the above pathways has drawbacks. For example, water soluble synthetic muramyl dipeptide tends to be rapidly excreted by the body and therefore renders the macrophages tumoridical for only a brief period. Lymphokine only activates the macrophages for three to four days after which the macrophages are resistant to reactivation. In animals it has been found that many of the drawbacks surrounding the activation of macrophages by lymphokine can be overcome by encapsulating the lymphokine within liposome.